Knowledge‐based representation: Patient engagement in drug development

Abstract Introduction Recently, different actors have intensified their efforts to make drug development more participatory. They have produced many frameworks, tools and dedicated fora, where patients are portrayed as relevant stakeholders to be involved throughout the entire drug development trajectory. To better understand what such participatory efforts entail, in this article, we investigate how patient representation is configured in drug development and what patients can engage as representatives in this field. Methods This is a qualitative study based on the thematic analysis of 40 semistructured interviews with different stakeholders in the field and three patient engagement How‐To guides (HTGs) complemented by observations of two sessions of the Patient Engagement Open Forum (PEOF) and a patient expert training of the European Patients' Academy on Therapeutic Innovation (EUPATI). Findings The emerging practices of patient engagement in drug development configure representation as hinging upon three types of knowledge—drug development knowledge, autobiographical knowledge and community knowledge—and a specific set of skills. We discern a new kind of representation based on these findings, termed ‘knowledge‐based representation’, which appears to more accurately describe how patients are expected to represent others in drug development. Conclusion Even though knowledge‐based representation may be understood as an attempt to downplay the political aspects of representation in favour of its epistemic elements, the political processes involved in patient representation in drug development cannot be ignored. The extent to which reliance on knowledge‐based representation will contribute to democratic decision‐making is likely to depend on the resources needed to develop the types of knowledge relevant to representation work and on how these types of knowledge are determined. Patient or Public Contribution Patient representatives and practitioners in the field of patient engagement (including 13 interviewees, representatives of EUPATI and HTG developers) gave feedback on the interpretation of the findings during a multistakeholder workshop we organised. We also sent an interviewee an extended draft and discussed it during an online meeting. Claudia Egher presented these findings at a PEOF session in June 2023, which further contributed to their validation.

2][13] Against this background, this paper aims to (1) gain insight into who can become patient representatives and (2) explore the implications of how representation is conceived for shaping PE in drug development.

| Theoretical framework: Representation and its challenges
The so-called 'standard approach' to representation conceives of representation as a dyadic, unidirectional principal-agent relationship, whereby a unified group elects representatives to act on its behalf. 11,14,15The representatives are expected to have knowledge about their constituencies' interests and to adopt policies that correspond to them, that is, to behave as their constituencies would. 16This perspective embraces a realist take on the interests of a constituency, as it assumes that they are available and stable.
Furthermore, these interests are assumed to develop according to general demographic factors, such as age, gender and ethnicity.
p.2Constructivist scholars have argued that preferences cannot be directly deduced from general demographic factors or shared experiences.Instead, preferences or social perspectives are shaped by an individual's life trajectory, the multiple groups s/he belongs to and the process of political mobilisation itself.
As the constituencies' preferences are understood to co-emerge in the process of representation, individuals become representatives through their direct experiences and efforts to articulate an issue.This paper draws upon the constructivist approach to analyse how patient representation is configured in drug development and who can act as representatives.[23] 2 | METHODS

| Study design
This is a qualitative study underpinned theoretically by a constructivist approach to representation.It relied on three avenues of data collection: semistructured interviews, document analysis and participant observations.Going beyond a single type of data was necessitated by the emerging and under-researched character of our field of study as well as by the complex and elusive nature of representation.Bringing together interviews, documents and observations allowed us to critically compare perspectives on representation and, thereby, elicit often tacit expectations regarding what makes for a good patient representative in the field of drug development.Interview-and document-based data were analysed using thematic content analysis, while observation data were used to enrich and better contextualise the resulting analysis.
The study was designed to be sensitive to the insights emerging in the process of research and to ensure adaptation to them by including additional participants and topics to explore.This in-built flexibility 24 allowed reaching depth and comprehensiveness in characterising representation.

| Data collection and participants
Since PE in drug development is a field shaped by many different actors as delineated in the Introduction, our data collection strategy focused on PFMD and EUPATI as multistakeholder groups where regulators, pharmaceutical companies and patient organisations collaborate.Such focus allowed bringing these diverse actors together analytically as stakeholders.PFMD and EUPATI were selected due to their prominence in terms of the volume of PE initiatives and intensity of collaborations.
The first avenue of data collection was semistructured interviews.Claudia Egher conducted 40 semistructured interviews with patient experts, patient advocates, patient education providers, members of the pharmaceutical industry and regulators, many of whom combined different roles from this list (for details see Table 1).
One repeat interview was conducted with a member of the EUPATI management team, with the two interviews focusing on the participant's two different roles.In several instances, more time was needed to complete the interviews than initially allocated, so another session was planned to complete it.Such sessions are indicated in Table 1 through the letter 'C' added to the interview number and together with initial interviews were counted as one.
To recruit participants for an interview, purposeful and snowball sampling were used.Members of PFMD and PFMD collaborators were first invited since PFMD is both a key international player in the field and a highly heterogeneous group in terms of actors involved.Snowball sampling was subsequently used, as the participants were asked to recommend other potential interviewees.Since PE in drug development is a relatively new field and not all information about key initiatives in the making is publicly available, snowball sampling allowed us to ensure that we did not overlook relevant participants.Importantly, since the initial interviews established the central relevance of EUPATI, EUPATI representatives were also contacted.These participants came mainly from European countries, with two participants from the United States, one from Australia and one from Zimbabwe.

| Data analysis and rigour
Data analysis started soon after the commencement of data collection and subsequently, the two proceeded simultaneously.
Interview-and document-based data were analysed through thematic content analysis. 25While the data were still being collected, the analysis proceded in the following way: we identified prominent themes in the data, we wrote analytical memos, and we discussed the themes and memos among the two of us as well as with the wider research group.In the process, patterns of meaning were delineated and critically assessed and additional questions requiring exploration were formulated and fed back into the data collection process.
Multiple such iterations took place until data saturation was reached, when limited new relevant insights, issues and topics were gained from new interviews.
Further, the coding was conducted using the software Atlas.allowing for more nuance and depth, and, ultimately, for triangulation, thus ensuring the robustness of the analysis. 26e findings were shared with the research participants and broader communities of stakeholders during a workshop on PE in drug development 27

| Autobiographical knowledge
Another important theme was the expectation for patient representatives in the field of drug development to be endowed with autobiographical knowledge.This is the knowledge that individual patients develop through their embodied experiences.It encompasses perspectives and insights through which a condition is made sense of at the level of one's entire life, based on one's values and preferences.Thus, autobiographical knowledge does not refer to the symptoms one experiences, or to the (side-)effects of medications in isolation, but to how they shape one's quality and trajectory of life.
Autobiographical knowledge was framed as unavailable to nonpatients and was used to highlight the insufficiency of insights that could be acquired from other types of representatives, as the following quote by a pharmaceutical company professional illustrates:

| Adaptive skills
The three delineated types of knowledge were expected to be The interviewees and the forum participants connected the patients' ability to represent others to their level of communication skills and practical experience.For example, a speaker at a PEOF session classified different levels of patient preparedness for engagement and, correspondingly, for representing others in the following way (Table 2).
Adaptive skills were thought to enable patients to correctly assess different participatory circumstances and to render them capable to resist situations marked by power imbalances, where they were expected to 'go, see, and shut up' (Toni Montserrat).At the same time, this set of skills was thought to enable patients to focus on what they could gain in lessthan-ideal situations.For instance, the trainees were advised that: 'Even if you don't like it, deal with the system in front of you, not with the one you'd want it to be.The latter you can pursue some other time, in other of the Patient Engagement Open Forum (PEOF) and a patient expert training of the European Patients' Academy on Therapeutic Innovation (EUPATI).

Findings:
The emerging practices of patient engagement in drug development configure representation as hinging upon three types of knowledge-drug development knowledge, autobiographical knowledge and community knowledge-and a specific set of skills.We discern a new kind of representation based on these findings, termed 'knowledge-based representation', which appears to more accurately describe how patients are expected to represent others in drug development.Conclusion: Even though knowledge-based representation may be understood as an attempt to downplay the political aspects of representation in favour of its epistemic elements, the political processes involved in patient representation in drug development cannot be ignored.The extent to which reliance on knowledgebased representation will contribute to democratic decision-making is likely to depend on the resources needed to develop the types of knowledge relevant to representation work and on how these types of knowledge are determined.Patient or Public Contribution: Patient representatives and practitioners in the field of patient engagement (including 13 interviewees, representatives of EUPATI and HTG developers) gave feedback on the interpretation of the findings during a 1.1 | Aims With the rise of enthusiasm for PE in drug development, it is important to examine how PE is being configured.Particularly, PE entails a few engaged patients speaking on behalf of or, in other words, representing, many others.Current scholarship and the emerging practice of PE in drug development tend to assume that such representation is unproblematic.Yet, political science and science and technology studies (STS) scholarship suggest that An interview guide was developed with a focus on topics, such as the interviewees' understanding of PE and the role of patient education for participation in drug development; who was included/ excluded from PE in drug development and how; how the interviewees engaged in PE and why; who and what they represented during PE activities; the quality of their interactions with other stakeholders and so forth.During the interviews, the participants were encouraged to also share insights they found relevant even if these were not included in the guide.Most interviews were conducted online (35), with five conducted in person during the EUPATI training.During both online and offline interviews, only Claudia Egher and the interviewee were present.All interviews were audio-recorded with the consent of the participants.The duration of the interviews varied between 45 and 180 min.To acknowledge interview participation as a form of labour, the interviewees whose direct quotes are provided in this article were allowed to decide on the level of anonymity they preferred upon reading the full manuscript.As a result, a combination of real names and pseudonyms is used, to respect both the wishes of the interviewees who wanted their contribution to be publicly acknowledged and of those who opted for anonymity.The second avenue of data collection was the collection of documents.The documents scrutinised were three How-To Guides (HTGs) published and promoted by PFMD between 2019 and 2021: How-to Guide for Patient Engagement in the Early Discovery and Preclinical Phases; How-to Guide on Patient Engagement in Clinical Trial Protocol Design; Plain language summaries (PLS) of Peer-Reviewed Publications and Conference Presentations: Practical 'How-To' Guide for Multi-stakeholder Co-creation.These documents were selected because their purpose was to shape PE during different phases of drug development and they were developed collaboratively by heterogenous groups of stakeholders.The third avenue of data collection was participant observation.Claudia Egher observed two online PEOF sessions (2022) and the EUPATI Patient Expert Training in Madrid (2022).A list of elements to focus on during the observations was developed based on insights from the literature and the interviews already conducted.This list was adjusted during the process of observation, to better fit the content and behaviours observed and to allow for the inclusion of unexpected relevant insights.Extensive field notes were taken during the observations.They contained Egher's impressions and descriptions of the participants' gestures and nonverbal behaviours as well as of the slides they used.
scheme was developed both deductively and inductively, being informed by the literature on representation and derived from the data.Definitions of and interrelations between all themes and subthemes were discussed and agreed upon by the authors.An overview of the coding scheme can be found in TableA1.Parts of interview transcripts and documents corresponding to different codes were examined by both authors together, to ensure agreement in interpretation.In several instances of disagreement, reasons for the (in)applicability of a certain code were discussed, invariably leading to an agreement.When the coding was completed, the fieldnotes taken by Egher during the observations were read and juxtaposed with the coded interviews and documents.The insights from all three data types were placed in a dialogue with each other,

3 | 3 . 1 |
FINDINGS Our analysis showed that patients are expected to possess three different types of knowledge-drug development knowledge, autobiographical knowledge, community knowledge-and what we call 'adaptive skills', to perform diverse representation work in drug development.Drug development knowledge Our findings revealed a shared expectation that patients need to be endowed with drug development knowledge to fruitfully contribute to new medications.The expected drug development knowledge consists of: a basic understanding of the drug development stages and familiarity with scientific terminology; insights into the organisation and practices of pharmaceutical companies; awareness of the main rules and regulations shaping the drug development process and the inner functioning of regulatory bodies.Patients were expected to be capable of engaging in different types of representation work depending on their level of proficiency.First, most interviewees expected patients with a basic level of drug development knowledge to be able to give feedback on and/or co-write materials, such as informed consent forms, clinical trial protocols and plain language summaries.Patients were thought to acquire this level of drug development knowledge through self-study, participation in clinical trials or short training, as the following quote by a patient representative illustrates: T A B L E 1 (Continued) Patient representatives were also expected to have community knowledge, which denotes insights about how a broad group of patients are affected by specific ill-health conditions.It was expected to be developed by people with autobiographical knowledge about a condition and those without.Even though autobiographical knowledge was thought to increase the legitimacy of the representative claims made by patient representatives endowed with community knowledge, community knowledge was expected to mitigate the risk that patient representatives might represent their own interests rather than those of broad groups.The following quote from a patient organisation staff member and education provider illustrates this: 'it is part of our mission to make sure that advocates have the kind of knowledge they need to think beyond their own personal experience' (Vivian Guillaumes).Community knowledge may thus be construed as both an epistemic and normative resource, ensuring the availability of knowledge about a community and adequate representation.Interestingly, we found no instances in our data where checks and balances regarding patient representation in drug development were openly discussed.Community knowledge was considered more time-sensitive than the types of knowledge discussed above, requiring frequent updates to remain relevant for representation work.It could be acquired by immersing oneself in already available data or by engaging in data collection in quantitative and qualitative ways.Whereas the collection and analysis of quantitative data were expected to lead to the construction of hierarchies of needs and preferences, acquiring community knowledge in qualitative ways was expected to ensure the latter's validity and relevance.Overall, community knowledge was expected to ensure a high level of correspondence between the hierarchy of needs and preferences put forward by the patients engaging in representation work and the experiences of their communities, as the following quote suggests: You need to understand your patients really well.(…) You can be versed in the research and hearing things through that by attending congresses and things, but you need to spend a little bit of time on the ground, so to speak, in order to really maintain that connection, and [so] that the information that you are providing is representative.(Anja Duval) Furthermore, community knowledge was expected to counteract the alienating effects that reaching a high level of proficiency in drug development knowledge might bring about between representatives and the groups they are meant to represent.
successfully used in patient representation in drug development, provided that the patient representatives were also endowed with what we call 'adaptive skills'.Adaptive skills function as a vehicle through which patients can perform representation work, as they help ensure that any type of representation work is found persuasive and legitimate.Adaptive skills denote capabilities that enable one to adjust to other stakeholders and environments and to make normative as well as pragmatic decisions to ensure the successful completion of one's representation work, as the following quote suggests: That's really important.You can know all about the phases of drug development, but when you're not able to work together as a team and also … look from the side of the other stakeholders, then you … cannot come to a compromise.(Alena Sapoznikov) Participant Observation Notes-271022).Furthermore, adaptive skills were also expected to allow patients to handle interactions that might challenge their own views and interests.In the context of the ongoing participatory turn in drug development, this study scrutinised how representation is configured in this field.Our findings show that patient representation in drug development is conceived as requiring drug development knowledge, autobiographical knowledge, community knowledge and adaptive skills.Variations in these types of knowledge and skills are linked to differences in the complexity of the representation work that patients are expected to be able to perform.Our findings point towards the emergence of a new kind of representation-knowledge-based representation.Knowledgebased representation denotes a process whereby representatives emerge as a result of the development of relevant epistemic resources that serve to legitimise the work they do on behalf of others.Thus, while it still focuses on one's ability to articulate representative claims, as in the work of constructivist scholars of representation, 13,28,29 knowledge-based representation foregrounds the types of knowledge that are needed for different claims to be considered representative.The notion of knowledge-based representation also differs from realist conceptualisations.First, representatives are not thought of as having access to stable and already available interests but are expected to engage in representation work based on domain-specific and varied types of knowledge that are viewed as necessary, even when the representatives and the represented share specific concerns and experiences.Second, representation is not understood as a monolithic endeavour consisting of similar actions.Instead, representation is conceived of as a diverse set of activities and behaviours of varying complexity and significance.Third, knowledgebased representation implies a more complex web of relationships than the unidirectional ones of the 'standard approach', 14 as patient representatives are expected to establish and maintain connections with diverse stakeholder groups at different moments and levels of their representation work in drug development.Reliance on a knowledge-based conception of representation has practical implications.For example, insistence on substantial levels of drug development knowledge may limit the diversity of patients who can perform representation work in drug development, as only those with enough free time, financial resources and determination to acquire such knowledge may become suitable candidates for engagement.The expectation of considerable adaptive skills may facilitate the formation of a small group of repeat participants in PE activities, as only a few patients might satisfy this expectation due to the significant amount of practice needed and these few patients would consequently be approached by multiple organisers.Thus, even though knowledgebased representation may be understood as an attempt to downplay the political aspects of representation in favour of its epistemic elements, the political processes involved in patient representation in drug development cannot be ignored.Whether or not this new type of representation will afford more democratic decision-making processes and under which conditions remains an open and intriguing question.

4. 1 |
Limitations and recommendationsOur study is confined to materials conveying recommendations and expectations.Future ethnographic studies are needed to understand how the expectations discussed here are enacted in different settings and at different stages in the drug development trajectory.As the materials we analysed have a European focus, additional research is needed to understand how patient representation in drug development is configured in other geographic areas.The findings of this study indicate that who can represent patients in drug development matters and point to the risk of the development of a narrow patient representative elite.We, therefore, recommend practitioners interested in ensuring the democratic character of patient representation in drug development to pay closer attention to the actors and methods involved in determining the types of knowledge needed for different representation work.Efforts should be made to facilitate the development of the types of knowledge relevant to representation in drug development among diverse patient groups.Furthermore, we recommend the development of a system of checks and balances to ensure the quality of patient representation in this field.T A B L E 2 Tiering expertise.
habits of a community: where members can be easily found, how they like to be approached Insights on differences and similarities in the therapeutic needs of potential subgroups of the community How to acquire community knowledge Through analysis of quantitative data collected by the patient organisation Through analysis of qualitative data collected by the patient organisation Conducting surveys on social media Talking to community members Developing communication channels for community members to share their needs, preferences and other relevant insights Representation activities based on community knowledge To explain statistics concerning patients' preferences To share insights about a community's therapeutic needs and preferences To ensure that a community's needs and preferences are taken into account by drug developer teams Representation-relevant risks Only some needs and preferences, experienced by subgroups of a community with whom one is familiar/by oneself are shared Distance between the representative and the community The same people acting as representatives Too time-consuming to develop and keep up-to-date Adaptive skills Components of adaptive skills Personality traits Communication/persuasive skills Ability to adjust to different environments Ability to correctly assess people and situations Ability to negotiate How to develop adaptive skills Reading relevant materials Participating in training activities Taking part in engagement activities Application of adaptive skills To successfully deploy one's knowledge To achieve one's/one's community/s goals To develop long-term relationships with relevant stakeholders Representation-relevant risks Lack or limited involvement of people with relevant knowledge, but with limited adaptive skills Limited diversity of representatives Limited opportunities to practically train this set of skills Sources of legitimacy Diversity of representatives Patient status of representatives (patients vs. nonpatients) At individual disease level versus broader disease category Gender of representatives Age of representatives Location of representatives Membership in a patient organisation Member of a patient organisation Not (necessarily) a member of a patient organisation (Continues) EGHER and ZVONAREVA | 11 of 12 T A B L E 1 Overview of interviewees.
Probably for the first year and a half, I just listened and didn't really know what was going on, or really understood the small parts of it.But gradually, as new trials were launched, the sponsors of those trials would get in touch with me, give me an explanation of it, and ask me if I would come on board.(…) So, I feel I could see that the HIV movement has really produced such knowledgeable patient advocates who are able to step into conversations with researchers … These conversations are about clinical trials and really detailed information about how treatments are developed.I see that the power of patient advocacy at its best is when a person is informed, trained, and able to speak at the same level as the researcher.(Maria Dutarte) Achieving this level of drug development proficiency was, however, thought to require specialised and intensive training.knowledge was always necessary for patients to represent others in drug development: This is another discussion we had with W [another patient education provider] and some patient groups who insisted that only experienced 'patient experts', and by making sense of the priorities and preferences the researchers identified using quantitative approaches.
you are talking about two symptoms, one symptom is pain.The HCPs [health care professionals] can never reflect the pain the patient feels, because they are not feeling the pain.Another symptom is itch.How do you ways that echo realist approaches to representation, this expectation relies upon the assumption that bodily states would be similarly experienced by different patients.Autobiographical knowledge was further expected to enable patients to perform representation work by assisting researchers in the early stages of drug development, by providing thick descriptions of their lives with a condition Developed based on a presentation titled 'Fair Market Value and PE' given by a speaker at a PEOF session on 23 February 2022.T A B L E A1 Overview of the main coding scheme.To describe in detail one's experiences with a condition that is not sufficiently addressed through available treatmentsTo describe in detail one's treatment needs that are not currently fulfilledTo indicate the benefits-side effects ratio one would find acceptable concerning new treatments Insights about the therapeutic needs and preferences of a communityInsights about contextual factors that inform the therapeutic needs of a community